Systems and approaches for sterilizing a drug delivery device

ABSTRACT

An on-body injector system includes a drug container assembly including a container, a seal member, and a sealing interface between the seal member and the container. The container includes an opening and the seal member at least partially covers the opening in the container. A fluid pathway assembly is coupled to the drug container assembly and includes a needle that is movable between a storage position, in which a point of the needle is spaced from the seal member, and a delivery position, in which the point of the needle is disposed at least partially through the seal member. A radiation generator is configured to emit rays of radiation to sterilize and/or disinfect the sealing interface. A barrier is disposed adjacent to the sealing interface and has an opening. At least a portion of the drug container assembly is positioned adjacent to the opening in the barrier.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation of U.S. patent application Ser. No. 16/179,399,filed Nov. 2, 2018, which claims the priority benefit of U.S.Provisional Patent Application No. 62/581,379, filed Nov. 3, 2017, theentire contents of which are hereby incorporated herein by reference.

FIELD OF THE DISCLOSURE

The present disclosure generally relates to drug delivery devices and,more particularly, to enabling a sterile drug container assembled withina drug delivery device.

BACKGROUND

Drug delivery devices, such as injectors, are used to deliver liquiddrugs to a patient. Upon activation, a drug delivery device will expel adrug stored within an internal reservoir through a needle, cannula, orother delivery member into the patient. Certain drug delivery devicesare manufactured with an empty reservoir, and the patient or healthcareprovider (e.g., a doctor, nurse, healthcare assistant, etc.) will fillthe reservoir with the drug at the time of use. Typically, this requiresthe patient or healthcare provider to operate a syringe to inject thedrug into the empty reservoir through an inlet port formed in the drugdelivery device. Prior to this filling procedure, the inlet port shouldbe sterilized by swabbing its outer surface with an alcohol wipe, forexample. Alternatively, certain drug delivery devices are installed witha pre-filled drug container by the patient or healthcare provider at thetime of use. Before installing the pre-filled drug container, matingconnectors disposed on, respectively, the pre-filled drug container anda fluid pathway assembly within the device should be sterilized, forexample, by swabbing them with an alcohol wipe. In either case, the drugdelivery device must be prepared by the patient or healthcare providerprior to use.

More recently, drug delivery devices have become available which arepre-assembled with a pre-filled drug container. This alleviates thepatient or healthcare provider from having to add the drug to the drugdelivery device at the time of treatment. In such drug delivery devices,a sterile fluid flow path is established between the pre-filled drugcontainer and a fluid pathway assembly upon activation of the device.Generally, this involves accessing an interior of the drug containerwith a container access needle such that the drug can be expelled fromthe container via the container access needle. Prior to activation ofthe device, the container access needle should be maintained in asterile condition so that the container access needle does not introducecontaminants into the container upon activation of the device. In someapproaches, existing assemblies for creating a sterile environment forthe drug container may be incapable of adequately sterilizing requiredcomponents and/or desired surfaces. For example, a gaseous sterilizingmixture (such as, for example ethylene oxide and/or saturated steam) maybe incapable of adequately penetrating or permeating through componentsin order to adequately sterilize certain components. In other examples,some existing approaches may also negatively impact the appearance orstructural integrity of the container, or alternatively may adverselyimpact the drug itself. In these examples, a user or healthcare providermay need to visually inspect the device to ensure that there are nopotentially hazardous contaminants in the container. In the event thatthe appearance and/or structural integrity of the container may becompromised, it may be difficult or impossible to conduct visualinspections, and thus, containers may be preemptively unnecessarilydisposed of.

The present disclosure sets forth systems and approaches forsterilization of drug delivery devices and related methods of assemblyand sterilization embodying advantageous alternatives to existingsterilization systems and methods, and that may address one or more ofthe challenges or needs mentioned herein, as well as provide otherbenefits and advantages.

SUMMARY

One aspect of the present disclosure provides a drug delivery devicethat includes a housing defining at least one opening, a containerassembly having first and second ends, an elongated portion extendingtherebetween, and an electron beam generator disposed near the housing.The container assembly includes a container having a container contactregion at the second end and an inner volume to contain a medicament, aseal member having a seal member contact region to form a sealingsurface with the container contact region, and a coupling device adaptedto sealingly couple the seal member to the container. The containerassembly is at least partially disposed in the opening such that thesecond end of the container is exposed through the housing. The electronbeam generator generates a sterilizing beam that penetrates the sealmember to sterilize the sealing surface.

In some examples, the at least one opening is defined by at least oneblocking region disposed near the container assembly. This blockingregion prevents the sterilizing beam from contacting the elongatedportion of the container or the inner volume of the container. In someexamples, the at least one blocking region may include a first blockingregion and a second blocking region disposed adjacent to the firstblocking region. The first blocking region may define a first diameterof the at least one opening, and the second blocking region may define asecond diameter of the at least one opening. The first diameter may beless than the second diameter to restrict the sterilizing beam fromprogressing in a direction that is parallel to the elongated portion ofthe container. Further, the second blocking region may be dimensioned torestrict the sterilization beam from progressing in a direction that isnon-orthogonal to the elongated portion of the container.

In some approaches, the second end of the container includes a shoulderregion. The housing may form a ledge adjacent to the shoulder region torestrict progression of the sterilization beam. In these and otherapproaches, the container may be constructed from a glass materialand/or a polymeric material.

The coupling device may be in the form of a crimp ring that compressesthe seal member towards the container. In some examples, the seal membercontact region may include an angled portion that engages the containercontact region to create a seal.

In some forms, the electron beam generator may generate electronic beamirradiation or, if configured to do so, x-rays. The sterilizing beam mayhave an energy level between approximately 0.3 MeV and approximately 5MeV. Additionally the housing may be constructed from a material ormaterials with atomic elements which all have low atomic numbers (e.g.elements such as aluminum, ceramic like boron nitride, or polymers likepolyethethylene, acrylonitrile butadiene styrene, etc.).

A second aspect of the present disclosure provides a method ofsterilizing a drug delivery assembly and includes providing a containerhaving a first end, a second end, an elongated portion extending betweenthe first end and the second end, a container contact region at or nearthe second end, and an inner volume adapted to contain a medicament tobe administered to a user. The container contact region is covered witha seal member having a seal member contact region such that the sealmember contact region and the container contact region form a sealingsurface. The seal member is sealingly coupled to the container using acoupling device. A portion of the container is disposed into an openingdefined by a housing such that the second end is exposed through thehousing. Using a sterilizing beam positioned near the housing thatpenetrates the seal member and/or the coupling device, the sealingsurface is sterilized.

A third aspect of the present disclosure provides a shield member forsterilizing a drug delivery container. The shield member includes afirst portion and a second portion. The first portion includes a firstsurface, a second surface, and a first elongated channel extendingbetween the first surface and the second surface. The second portionincludes a first surface coupled to the first portion and an interiorregion. The first surface of the second portion defines a secondelongated channel extending into the interior region. The firstelongated channel and the second elongated channel cooperate to form areceptacle for a drug delivery container and to form a blocking regionto restrict a sterilizing beam from progressing in a direction along thefirst elongated channel or the second elongated channel.

BRIEF DESCRIPTION OF THE DRAWINGS

The above needs are at least partially met through provision of the flowadapter for a drug delivery device described in the following detaileddescription, particularly when studied in conjunction with the drawings,wherein:

FIG. 1 illustrates a schematic cross-sectional view of an embodiment ofa drug delivery device in accordance with various embodiments;

FIG. 2A illustrates a cross-sectional exploded view of an examplecontainer assembly of the example drug delivery device of FIG. 1 inaccordance with various embodiments;

FIG. 2B illustrates a cross-sectional assembled view of a storage stateof the container assembly of FIG. 2A in accordance with variousembodiments;

FIG. 2C illustrates a cross-sectional assembled view of a delivery stateof the container assembly of FIGS. 2A and 2B in accordance with variousembodiments;

FIG. 3 illustrates a perspective assembled view of the containerassembly of FIGS. 2A-2C in accordance with various embodiments;

FIG. 4 illustrates a zoomed cross-sectional assembled view of thecontainer assembly of FIGS. 2A-3 in accordance with various embodiments;

FIG. 5 illustrates a cross-sectional assembled view of the containerassembly disposed within a housing in accordance with variousembodiments;

FIG. 6 illustrates a cross-sectional assembled view of an alternativecontainer assembly and housing in accordance with various embodiments;

FIGS. 7A and 7B illustrate perspective views of a housing to accommodateone or more container assemblies in accordance with various embodiments;

FIGS. 8 and 9 illustrate perspective and cross-sectional views,respectively, of an alternative embodiment of a shielding member inaccordance with the principles of the present disclosure; and

FIGS. 10 and 11 perspective and cross-sectional views, respectively, ofanother alternative embodiment of a shielding member in accordance withthe principles of the present disclosure.

Skilled artisans will appreciate that elements in the figures areillustrated for simplicity and clarity and have not necessarily beendrawn to scale. For example, the dimensions and/or relative positioningof some of the elements in the figures may be exaggerated relative toother elements to help to improve understanding of various embodimentsof the present invention. Also, common but well-understood elements thatare useful or necessary in a commercially feasible embodiment are oftennot depicted in order to facilitate a less obstructed view of thesevarious embodiments. It will further be appreciated that certain actionsand/or steps may be described or depicted in a particular order ofoccurrence while those skilled in the art will understand that suchspecificity with respect to sequence is not actually required. It willalso be understood that the terms and expressions used herein have theordinary technical meaning as is accorded to such terms and expressionsby persons skilled in the technical field as set forth above exceptwhere different specific meanings have otherwise been set forth herein.

DETAILED DESCRIPTION

The present disclosure generally relates to systems and approaches forsterilizing a container for a drug delivery device. Generally, thecontainer is coupled to a stopper and a crimping device to form a sealedunit and the sealed unit is disposed within a shield member. ElectronBeam (referred to as “E-Beam”) Irradiation is applied to the sealed unitto sterilize a contact surface between the container and the stopperwhich is contained within the crimping device. By advantageously relyingon the geometry of the sealed unit and the shield member, suitableirradiation may reach the contact surface for the purpose of providingsterilization, while the shield member, the crimping device, and/or thestopper may act, individually or cooperatively, to limit penetration ofthe irradiation beams, that is, to avoid exposing the container and drugcontacting surfaces to ionizing irradiation that could impact itsphysical, chemical, or aesthetic attributes. As such, the irradiation isshielded from the remainder of the container, thereby reducing and/oreliminating the potential for discoloration to the container, the drugthat may be contained therein, and/or any other components. As a result,a user may properly inspect the contents of the container prior to drugadministration, thereby reducing the number of unnecessarily disposedcontainers.

FIG. 1 is a schematic illustration of one embodiment of a drug deliverydevice 10 constructed in accordance with principles of the presentdisclosure. The drug delivery device 10 may be operated tosubcutaneously or transdermally deliver a drug to a patient. In theillustrated embodiment, the drug delivery device 10 is configured as awearable drug delivery device, such as an on-body injector or anambulatory infusion pump, and is releasably attachable to the patient'stissue 11 (e.g., the patient's skin). In other embodiments (notillustrated), the drug delivery device 10 may be configured as apen-type injector, such as an autoinjector or injection pen, which istemporarily held against the patient's tissue 11 over the course of theinjection. The drug delivery device 10 may be configured toautomatically deliver a fixed or a patient/operator-settable dose of thedrug over a controlled or selected period of time. Furthermore, the drugdelivery device 10 may be intended for self-administration by thepatient, or may be operated by a formally trained healthcareprofessional or other caregiver to administer the injection.

Generally, the drug delivery device 10 may include an insertionmechanism 12, a container assembly 14 including a container 15, a fluidpathway assembly 22, a drive mechanism 24, and a controller 26, each ofwhich may be disposed within an interior space of a main body 29. Anactuator 28 (e.g., a user-depressible button, touchscreen, microphone,etc.) may protrude through or otherwise be disposed at an exteriorsurface of the body 29 and may be configured to initiate operation ofthe drug delivery device 10 by activating, via mechanical and/orelectrical means (shown in dotted lines in FIG. 1), the insertionmechanism 12, the fluid pathway assembly 22, the drive mechanism 24, thecontroller 26, and/or other mechanisms and/or electronics. Inembodiments where the actuator 28 is a button that is depressed orotherwise physically moved by a user or patient, the actuator 28 may beconfigured to exert a motive force needed to activate the insertionmechanism 12, the fluid pathway assembly 22, the drive assembly 24, thecontroller 26, and/or other mechanisms. In such embodiments, theactuator 28 may be physically connected to, either directly orindirectly via a mechanical linkage, the insertion mechanism 12, thedrive mechanism 24, the fluid pathway assembly 22, and/or othermechanisms such that manually depressing or otherwise interacting withthe actuator 28 supplies the motive force necessary to activate theinsertion mechanism 12, the drive mechanism 24, the fluid pathwayassembly 22, and/or other mechanisms. For example, in some embodiments,manually depressing the actuator 28 may cause the fluid pathway assembly22 to move towards the stationary container assembly 14, or cause thecontainer assembly 14 to move towards the stationary fluid pathwayassembly 22, and thereby cause a container access needle to penetratethrough a seal member into a reservoir or interior volume of thecontainer assembly 14. Additionally or alternatively, the actuator 28may operate as an input device that transmits an electrical and/ormechanical signal to the controller 26, which in turn may executeprogrammable instructions to control operation of the insertionmechanism 12, the drive mechanism 24, the fluid pathway assembly 22,and/or other mechanisms. In such embodiments, the controller 26 mayinclude a processor (e.g., a microprocessor) and a non-transitory memoryfor storing the programmable instructions to be executed by theprocessor. Furthermore, in such embodiments, the drug delivery device 10may include an internal actuator (e.g., an electric motor, a pneumaticor hydraulic pump, and/or a source of pressurized gas or liquid) whichis separate from the actuator 28 and which, in response to an electricalcontrol signal received from the controller 26, exerts the motive forceneeded to activate the insertion mechanism 12, the drive mechanism 24,the fluid pathway assembly 22, and/or other mechanisms.

The body 29 may include a bottom wall 25 configured to be releasablyattached (e.g., adhered with an adhesive) to the patient's tissue 11,and a top wall 27 including one or more visual indicators 42 (e.g.,lights, graphical displays, etc.) and/or a window 35 for viewing thecontainer 15 and a drug 32 contained therein. The one or more visualindicators 42 may be used to communicate information to the user aboutthe operational state of the drug delivery device 10 and/or thecondition of the drug 32. An opening 31 may be formed in the bottom wall25, and optionally a pierceable sterile barrier 33, such as a pierceableseptum, may extend across the opening 31 to seal the interior of thebody 29 prior to use. In some embodiments, the pierceable sterilebarrier 33 may be omitted, and instead a removable sealing member (notillustrated) may cover and seal close the opening 31 prior to use.

More particularly with respect to the window 35, this element may beconstructed of a transparent or semi-transparent material and generallyaligned with the container 15, so as to allow a patient or user of thedrug delivery device 10 to inspect the drug 32 within the container 15and/or confirm dose completion. Suitable materials for constructing thewindow 35 include, but are not limited to, glass and/or plastic. Thelocation of the window 35 on the exterior of the drug delivery device 10may expose the drug 32 to ambient light including sunlight. Some drugsmay be sensitive to certain wavelengths of light and undergo undesirablemolecular changes when exposed to such wavelengths of light. Forexample, some drugs may be sensitive to wavelengths of light in theultraviolet (UV) range, the visible range, and/or the infrared range. Toprotect drugs that are primarily sensitive to light in the UV rangeand/or the infrared range, a dark tint may be added to the window 35and/or the window 35 may be dimensioned to cover a relatively smallsurface area of the body 29. For drugs that are primarily sensitive tolight in the visible range, it may not be necessary to add a dark tintto the window 35 and/or shrink the size of the window 35. Instead, thewindow 35 may be constructed with a polarized filter. In someembodiments, the polarized filter may be a film or other coating that isapplied to the window 35. In other embodiments, the polarized filter maybe integrated directly into the material of window 35. The polarizedfilter may allow for viewing and inspection of the drug 32 within thecontainer 15, while filtering out up to and including approximately(e.g., ±10%) 50% of light in the visible range. In some embodiments, theportion of visible light filtered out by the window 35 may fall in arange between approximately (e.g., ±10%) 0-50%, or 10-50%, or 20-50%, or25-50%, or 0-40%, or 0-30%, or 0-25%, depending on the photosensitivityof the drug 32 and/or the eye strength of the patient population of thedrug 32, among other considerations. Adding the polarized filter to thewindow 35, in lieu adding a dark tint to the window 35 and/or shrinkingthe size of the window 35, advantageously protects the drug 35 fromlight in the visible range without substantially compromising theability of the patient or user of the drug delivery device 10 to inspectthe drug 32 within the container 15.

After the bottom wall 25 of the body 29 is attached to the patient'stissue 13, the insertion mechanism 12 may be activated to move adelivery member from a retracted position within the body 29 to adeployed position extending outside of the body 29. In the presentembodiment, this may include the insertion mechanism 12 inserting atrocar 21 and a hollow cannula 23 surrounding the trocar 21 through thepierceable sterile barrier 33 and into the patient's tissue 11, asillustrated in FIG. 1. Immediately or shortly thereafter, the insertionmechanism 12 may automatically retract the trocar 21, leaving the distalopen end of the cannula 23 inside the patient for subcutaneous deliveryof the drug 32. The trocar 21 may be solid and have a sharpened end forpiercing the patient's skin 11. Furthermore, the trocar 21 may be madeof a material that is more rigid than the cannula 23. In someembodiments, the trocar 21 may be made of metal, whereas the cannula 23may be made of plastic or another polymer. The relative flexibility ofthe cannula 23 may allow it to be disposed subcutaneously within thepatient's tissue 11 for a period of a time without causing pain orsignificant discomfort to the patient. In other embodiments (notillustrated), the trocar 21 and cannula 23 may be omitted, and insteadthe insertion mechanism 12 may insert only a rigid, hollow needle intothe patient for subcutaneous delivery of the drug 32.

In some embodiments, the insertion mechanism 12 may include one or moresprings (e.g., coil springs, torsion springs, etc.) initially retainedin an energized state, and which are released upon depression of theactuator 28 in order to insert the trocar 21 and cannula 23, or hollowneedle, into the patient. Furthermore, retraction of the trocar 21 maybe achieved by the automatic release of another spring after the trocar21 and cannula 23 have been inserted into the patient. Other powersources for insertion and/or retraction are possible, including, forexample, an electric motor, a hydraulic or pneumatic pump, or a canisterthat releases a pressurized gas or pressurized liquid to provideactuation energy.

With reference to FIGS. 1-2C, the container assembly 14 includes acontainer 15, which in some contexts may be referred to as a primarycontainer, a seal member 40, and a coupling device 91. The containerassembly 14 may include a proximal or first end 36 and a distal orsecond end 37 at which the seal member 40 and the coupling device 91 arepositioned. The container 15 has an elongated portion or wall 38extending between the first end 36 and the second end 37. The wall 38has an interior surface 43 defining an inner volume or reservoir 30 thatis filled with the drug 32 and further may have an exterior surface 47.In some embodiments, the reservoir 30 may be pre-filled with the drug 32by a drug manufacturer prior to installation of the container 15 in thedrug delivery device 10. In some embodiments, the container 15 may berigidly connected to the body 29 such that the container 15 cannot moverelative to the housing; whereas, in other embodiments, the container 15may be slidably connected to the body 29 such that the container 15 canmove relative to the body 29 during operation of the drug deliverydevice 10. The container 15 may have an elongate, barrel-like orcylindrical shape extending along a longitudinal axis A. In embodimentswhere the drug delivery device 10 is configured as an on-body injector,the longitudinal axis A of the container 15 may be perpendicular orsubstantially perpendicular, or otherwise non-parallel, to a directionin which the insertion mechanism 12 inserts a delivery member such asthe cannula 23 into the patient. This configuration may allow theon-body injector to have a generally planar, low-profile shape that canbe worn by the patient without impeding the patient's movement.Initially, a stopper 34 or other piston member may be positioned in thereservoir 30 at the proximal or first end 36 of the container 15. Thestopper 34 may sealingly and slidably engage the interior surface 43 ofthe wall 38 of the container 15, and may be movable relative to the wall38 of the container 15.

The volume of the drug 32 contained in the reservoir 30 prior todelivery may be: any volume in a range between approximately (e.g.,±10%) 0.5-20 mL, or any volume in a range between approximately (e.g.,±10%) 0.5-10 mL, or any volume in a range between approximately (e.g.,±10%) 1-10 mL, or any volume in a range between approximately (e.g.,±10%) 1-8 mL, or any volume in a range between approximately (e.g.,±10%) 1-5 mL, or any volume in a range between approximately (e.g.,±10%) 1-3.5 mL, or any volume in a range between approximately (e.g.,±10%) 1-3 mL, or any volume in a range between approximately (e.g.,±10%) 1-2.5 mL, or any volume in a range between approximately (e.g.,±10%) 1-2 mL, or any volume equal to or less than approximately (e.g.,±10%) 4 mL, or any volume equal to or less than approximately (e.g.,±10%) 3.5 mL, or any volume equal to or less than approximately (e.g.,±10%) 3 mL, or any volume equal to or less than approximately (e.g.,±10%) 2.5 mL, or any volume equal to or less than approximately (e.g.,±10%) 2 mL, or any volume equal to or less than approximately (e.g.,±10%) 1.5 mL, or any volume equal to or less than approximately (e.g.,±10%) 1 mL. The reservoir 30 may be completely or partially filled withthe drug 32. The drug 32 may be one or more of the drugs describedbelow, such as, for example, a granulocyte colony-stimulating factor(G-CSF), a PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9)specific antibody, a sclerostin antibody, or a calcitonin gene-relatedpeptide (CGRP) antibody.

During operation of the drug delivery device 10, the drive mechanism 24may push the stopper 34 along the longitudinal axis A from the proximalend 36 of the container 15 to the distal end 37 of the container 15 inorder to expel the drug 32 from the container 15. In some embodiments,the drive mechanism 24 may include one or more springs (e.g., coilsprings, torsion springs, etc.) initially retained in an energizedstate, and which are released upon depression of the actuator 28.Following their release, the spring(s) may expand or contract to movethe stopper 34 through the reservoir 30 along the longitudinal axis Afrom the proximal end 36 of the container 15 to the distal end 37 of thecontainer 15. In other embodiments, the drive mechanism 24 may includean electric motor (not illustrated) which rotates a gear mechanism,including for example one or more sprocket gears, to cause axial motionof the stopper 34 through the reservoir 30. In still furtherembodiments, the drive mechanism 24 may include both an electric motorand spring(s), wherein the electric motor regulates expansion of thespring(s) via a tether or pulley system. In still further embodiments,the drive mechanism 24 may include a canister that releases apressurized gas or pressurized liquid to provide actuation energy.

At the distal end 37 of the container 15, an opening 45 (see FIG. 2A)may be formed in a container contact region or distal end surface 72(see FIG. 2A) of the wall 38. The container contact region 72 may definea portion of the exterior surface 47 of the wall 38. At least prior tooperation of the drug delivery device 10, the opening 45 may be coveredand sealed closed by the seal member 40, such as a pierceable septum,connected to the distal end 37 of the container 15. The seal member 40may include a proximal end surface 73, a seal member contact region 74,and a distal end surface 75. The proximal end surface 73 of the sealmember 40 and the interior surface 43 of the wall 38 of the container 15may define the reservoir 30. Additionally, in some embodiments, a distalend surface 39 of the stopper 34 may define the reservoir 30.

Generally, the seal member 40 may be configured to selectively permitaccess to the reservoir 30. During operation, the seal member 40 may bephysically altered (e.g., pierced) to permit access to and fluidcommunication with the drug 32 in the reservoir 30. In some embodiments,the seal member 40 may be constructed of a flexible or elasticallydeformable material such as rubber, for example, which is capable ofbeing penetrated or pierced by a sharpened end or point 63 of acontainer access needle 60 of the fluid pathway assembly 22. In someembodiments, the seal member 40 may be clamped or otherwise secured tothe container contact region 72 of the wall 38 by the coupling device 91(see FIG. 2B-FIG. 4) and/or adhered directly to the container contactregion 72.

Referring back to FIG. 1, fluid pathway assembly 22 may be configured toestablish fluid communication between the container 15 and the insertionmechanism 12 via a sterile fluid flow path during operation of the drugdelivery device 10. Prior to use of the drug delivery device 10, thefluid pathway assembly 22 may not be in fluid communication with thecontainer 15. During setup of the drug delivery device 10, or during theinitial stages of operation of the drug delivery device 10 prior to drugdelivery, the user may manually, or the drug delivery device 10 mayautomatically, enable, connect, or open the necessary connections toestablish fluid communication between the container 15 and the fluidpathway assembly 22. Subsequently, the drive mechanism 24 may move thestopper 34 in the distal direction to force the drug 32 stored in thecontainer 15 through the sterile fluid flow path of the fluid pathwayassembly 22 and into the cannula 23 or needle or other delivery memberof the insertion mechanism 12 for subcutaneous delivery to the patient.

In some embodiments, the fluid pathway assembly 22 may be rigidlyconnected to the body 29 of the drug delivery device 10 such that thefluid pathway assembly 22 cannot move relative to the housing; whereas,in other embodiments, the fluid pathway assembly 22 may be slidably ormoveably connected to the body 29 such that the fluid pathway assembly22 can move relative to the body 29 during operation of the drugdelivery device 10. In the former embodiments, the container 15 may beslidably or moveably connected to the body 29 such that the seal member40 can be moved toward and pierced by the point 63 of the stationarilyarranged container access needle 60 of the fluid pathway assembly 22. Inthe latter embodiments, the container 15 may be stationarily positionedwhile the fluid pathway assembly 22 is moved toward the container 15,causing the point 63 of the container access needle 60 to pierce throughthe seal member 40 and access the reservoir 30.

The fluid pathway assembly 22 may include a first end 44 connected tothe container 15, a second end 48 connected to the insertion mechanism12, and a fluid passage 50 extending between the first end 44 and thesecond end 48. As described in more detail below, in some embodimentsthe first end 44 of the fluid pathway assembly 22 may be connected tothe container 15 via a clip member 53. The fluid passage 50 may besterilized, and may be partially or entirely made of a flexible tubing52. Initially, there may be slack in the flexible tubing 52 to allow thefluid pathway assembly 22 to move relative to the body 29 and/or toallow components of the insertion mechanism 12 to which the fluidpathway assembly 22 is attached to move relative to the body 29. In someembodiments, the fluid passage 50 may include a rigid fluid restrictorelement (not illustrated) in addition to the flexible tubing 52. Thefluid restrictor element may have a smaller inner diameter than that ofthe flexible tubing 52 in order to regulate the flow rate of the drug 32as it passes through the fluid pathway assembly 22. Furthermore, thefluid restrictor element may be made of a more rigid material than theflexible tubing 52. For example, the fluid restrictor element may bemade of metal, whereas the flexible tubing 52 may be made of a polymericmaterial such as plastic.

Still referring to FIG. 1, the first end 44 of the fluid pathwayassembly 22 may include the container access needle 60 and an overmoldmember 62. In general, the overmold member 62 may serve as a mountingmember or connection hub for the container access needle 60 and providea portion of the container access needle 60 which does not access thereservoir 30 with an enlarged outer dimension, such as an enlarged outerdiameter. The container access needle 60 may have a sharpened end orpoint 63, corresponding to a proximal end of the container access needle60, and a distal end 64 in fluid communication with the fluid passage50. In the illustrated embodiment, the container access needle 60 has abend such that the point 63 of the container access needle 60 may beaxially aligned with the longitudinal axis A of the container 15 whereasthe distal end 64 of the container access needle 60 may be perpendicularor otherwise non-parallel to the longitudinal axis A of the container15. The overmold member 62 may cover a length of the container accessneedle 60, including the bend, with the point 63 of the container accessneedle 60 protruding outwardly from a proximal end 65 of the overmoldmember 62. As shown in FIG. 1, a distal end 66 of the overmold member 62may include a mouth or opening that allows an end of the flexible tubing52 to be inserted into the overmold member 62. In alternativeembodiments, the distal end 66 of the overmold member 62 may be insertedinto an opening formed in the end of the flexible tubing 52.

The container access needle 60 may possess a hollow, tubular shape withone or more openings at each of the point 63 and the distal end 64. Thecontainer access needle 60 made be constructed of a rigid materialincluding, but not limited to, metal (e.g., stainless steel) and/orplastic. In some embodiments, the overmold member 62 may be constructedof a different material than the container access needle 60 such thatthe overmold member 62 and the container access needle 60 are separate,but rigidly connected components. In some embodiments, the overmoldmember 62 may be constructed of a rigid plastic material whereas thecontainer access needle 60 is constructed of metal. In otherembodiments, the overmold member 62 and the container access needle 60may be made of the same material such that they form a single, unitaryone-piece structure.

Generally, the overmold member 62 may have a sleeve-like or tubularshape that surrounds a length of the container access needle 60. Theovermold member 62 may be fixedly or rigidly connected to the needle 60such that the overmold member 62 and the needle 60 can move togetherjointly as a single unit or structure. Stated another way, the overmoldmember 62 may be fixedly or rigidly connected to the container accessneedle 60 such that the needle 60 is prevented from moving relative tothe overmold member 62. In some embodiments, the fixed or rigidconnection between the overmold member 62 and the container accessneedle 60 may be achieved by having the material of the overmold member62 bond to the material of the container access needle 60. Such bondingmay be achieved by forming the overmold member 62 around the containeraccess needle 60 by way of an overmolding or insert molding process. Insome such embodiments, the container access needle 60 may be placed in amold and subsequently a melted plastic, or other melted material, may bepoured or injected into the mold and allowed to solidify to form theovermold member 62. Other processes for manufacturing the overmoldmember 62 are possible as well. In alternative embodiments, the overmoldmember 62 may be formed with a through hole or passage extending betweenthe proximal and distal ends 65 and 66 and subsequently the containeraccess needle 60 may be inserted into this through hole or passage. Insuch embodiments, the container access needle 60 may be secured to theovermold member 62 via, for example, an interference-fit connection, anadhesive, and/or a fastener.

At least the proximal end 65 of the overmold member 62 may flushly covera length of the container access needle 60 with no gaps therebetween. Asseen in FIG. 1, there may be a gap between the distal end 66 of theovermold member 62 and the container access needle 60 to form the mouthor opening for receiving the flexible tubing 52. In alternativeembodiments, no mouth or opening may be formed in the distal end 66 ofthe overmold member 62 such that the no gap exists between the distalend 66 of the overmold member 62 and the container access needle 60.

As shown in FIG. 1, and described below in more detail with reference toFIGS. 2A-2C, prior to activation of the drug delivery device 10 (e.g.,in a storage state), the overmold member 62 may define an enclosed cleanspace 68 between the overmold member 62 and the seal member 40. In someembodiments, the enclosed clean space 68 may be an empty space which hasbeen sterilized and which may or may not be a vacuum. In otherembodiments, the enclosed clean space may be a space filled with agaseous or liquid sterilizing agent. In the embodiment illustrated inFIGS. 1-2C, a boundary (e.g., a sterile boundary) of the enclosed cleanspace 68 may be defined solely by an exterior surface 77 of the overmoldmember 62 and an interior surface 79 of the seal member 40. However, theboundary of the enclosed clean space 68 may not to be limited tosurfaces of overmold member 62 and the seal member 40. In someembodiments, an O-ring (not illustrated) may be disposed around theproximal end 65 of the overmold member 62 such that the boundary of theenclosed clean space 68 is defined by an exterior surface of the O-ringin addition to the exterior surface 77 of the overmold member 62 and theinterior surface 79 of the seal member 40. In still further embodiments,the boundary of the enclosed clean space 68 may be defined by aninterior surface of the clip member 53, an O-ring disposed around theproximal end 65 of the overmold member 62, and the distal end surface 75of the seal member 40. Other configurations are also possible fordefining the boundary of the enclosed clean space 68.

As shown in FIGS. 1 and 2B, prior to activation of the drug deliverydevice 10, the container access needle 60 may be arranged in a storageposition with its point 63 disposed exterior to the reservoir 30. Insome embodiments, in the storage position, the point 63 of the containeraccess needle 60 may be disposed in the enclosed clean space 68, therebyinhibiting or preventing contamination of the point 63 of the containeraccess needle 60. In other embodiments, in the storage position, thepoint 63 of the container access needle 60 may be disposed partiallythrough the seal member 40 such that the point 63 is embedded within thematerial of the seal member 40. Embedding the point 63 within thematerial of the seal member 40 may inhibit or prevent contamination ofthe point 63. In some embodiments, the enclosed clean space 68 may befilled with a gaseous or liquid sterilizing agent, such that duringmanufacturing, when the point 63 is inserted through the enclosed cleanspace 68, the point 63 is sterilized by the gaseous or liquidsterilizing agent.

In order to restrain the container access needle 60 in the storageposition prior to activation of the drug delivery device 10, the clipmember 53 may frictionally engage the exterior surface 77 of theovermold member 62. Accordingly, the clip member 53 may resist movementof the overmold member 62 in a direction toward and/or away from theseal member 40.

As illustrated in FIG. 2C, upon activation of the drug delivery device10, the container access needle 60 may be moved from the storageposition to a delivery position, where the point 63 is disposed throughthe proximal end surface 73 of the seal member 40 and into the reservoir30, thereby establishing fluid communication with the reservoir 30optionally containing the drug 32. In some embodiments, the actuator 28may be mechanically linked or connected, directly or indirectly, to thecontainer access needle 60 such that manual depression of the actuator28 provides the motive force necessary for moving the container accessneedle 60 from the storage position to the delivery position 62. Inother embodiments, as described above, an energized actuator (including,e.g., an electric motor, a pneumatic or hydraulic pump, and/or a sourceof pressurized gas or liquid) may be activated in response to a user'sdepression of the actuator 28 and provide the motive force necessary formoving the container access needle 60 from the storage position to thedelivery position.

Where appropriate, any of the above-described sub-assemblies,mechanisms, components, features, functionalities, methods ofmanufacture, methods of use, and other aspects of the drug deliverydevice 10 may be replaced with and/or combined with any of thesub-assemblies, mechanisms, components, features, functionalities,methods of manufacture, methods of use, and other aspects of the drugdelivery devices described in some or all of the following documents,each of which is hereby incorporated by reference in its entirety forall purposes: U.S. Pat. No. 9,061,097; U.S. Patent ApplicationPublication No. 2017/0124284; U.S. Patent Application Publication No.2017/0119969; U.S. Patent Application Publication No. 2017/0098058; U.S.Patent Application Publication No. 2017/0124285; U.S. Patent ApplicationPublication No. 2017/0103186; U.S. Provisional Patent Application No.62/460,501 entitled “INSERTION MECHANISM FOR DRUG DELIVERY DEVICE”; U.S.Provisional Patent Application No. 62/469,226 entitled “INSERTIONMECHANISM FOR DRUG DELIVERY DEVICE”; U.S. Provisional Patent ApplicationNo. 62/468,190 entitled “INSERTION MECHANISM AND METHOD OF INSERTING ANEEDLE OF A DRUG DELIVERY DEVICE”; U.S. Provisional Patent ApplicationNo. 62/460,559 entitled “DRUG DELIVERY DEVICE WITH STERILE FLUIDFLOWPATH AND RELATED METHOD OF ASSEMBLY”; U.S. Provisional PatentApplication No. 62/294,842 entitled “DRUG DELIVERY DEVICE, METHOD OFMANUFACTURE, AND METHOD OF USE”; U.S. Provisional Patent Application No.62/297,718 entitled “DRUG DELIVERY DEVICE, METHOD OF MANUFACTURE, ANDMETHOD OF USE”; U.S. Provisional Patent Application No. 62/320,438entitled “DRUG DELIVERY DEVICE, METHOD OF MANUFACTURE, AND METHOD OFUSE”; International Patent Application No. PCT/US2017/017627 entitled“DRUG DELIVERY DEVICE, METHOD OF MANUFACTURE, AND METHOD OF USE”; andInternational Patent Application No. PCT/US2017/026524 entitled “DRUGDELIVERY DEVICE, METHOD OF MANUFACTURE, AND METHOD OF USE”.

Turning to FIGS. 2A-2C, illustrated is an enlarged view of the container15, the seal member 40, and part of the fluid pathway assembly 22 of thedrug delivery device 10 shown in FIG. 1. The container 15 may have agenerally cylindrical shape with a barrel portion occupying most of theproximal end 36, and a neck portion at its distal end 37. In thedepicted version, an inner diameter D1 of the distal end 37 neck portionis smaller than an inner diameter of the barrel portion. At the distalend 37 neck portion of the container 15, the wall 38 may protruderadially outwardly to define a container flange 70. The container flange70 and the wall 38 may be connected via a curved and/or angled shoulder76. The container flange 70 may extend partially or entirely around acircumference of the distal end 37 of the container 15. The containerflange 70 may define a container contact region 72 of the container 15,which is perpendicular or otherwise non-parallel to the longitudinalaxis A of the container 15 and generally faces in a distal direction.The opening 45 may be formed in the container contact region 72 andcommunicate with the reservoir 30 of the container 15. In someembodiments, the container flange 70 may be omitted such that thecontainer contact region 72 does not project radially outwardly of aremainder of the container 15. The wall 38 at the proximal end 36 of thecontainer 15 may include a proximal end surface 89, which isperpendicular or otherwise non-parallel to the longitudinal axis A ofthe container 15 and generally faces in a proximal direction. An opening99 may be formed in the proximal end surface 89 and communicate with thereservoir 30. The stopper 34 may inserted through the opening 99 intothe container 15. The container 15 may be constructed of glass, apolymeric material such as plastic, or any other suitably inert materialwhich is not likely to chemically interact with the drug 32.

Referring to FIG. 2A, the seal member 40 may be centrally aligned withthe longitudinal axis A of the container 15 when the seal member 40 isinserted into the container 15 such that the seal member 40 and thecontainer 15 share the same longitudinal axis A. The seal member 40 maybe divided by an imaginary plane perpendicular to the longitudinal axisA into a proximal (or bottom) end 80 and a distal (or top) end 82. Theproximal end 81 and the distal end 83 may each possess a generallycylindrical shape and have outer diameters D2 and D3, respectively, asseen in FIG. 2A. The distal end 83 may be enlarged relative to theproximal end 81, such that the outer diameter D3 (or other outerdimension) of the distal end 83 is larger than an outer diameter D2 (orother outer dimension) of the proximal end 81. A flange 84 of the sealmember 40 is defined by an outer peripheral (e.g., circumferential)portion of the distal end 83 of the seal member 40 that is disposedradially outwardly of the proximal end 81 of the seal member 40. Theseal member contact region 74 is at least partially formed by the flange84.

Referring to FIGS. 2B, 2C, and 4, when the seal member 40 is attached tothe container 15, the proximal end 81 of the seal member 40 may beinserted through the opening 45 into the reservoir 30 and the sealmember contact region 74 may directly contact and sealingly engage thecontainer contact region 72 of the container 15 to form a sealinginterface 72 a. As illustrated in FIG. 4, the seal member contact region74 may include an angled portion 74 a that may compress to help form afluid and/or airtight seal with the container contact region 72.

In some embodiments, the proximal end 81 of the seal member 40 mayinclude one or more radially outwardly protruding annular ribs 100 forsealingly engaging the inner surface 43 of the wall 38 of the container15. The annular rib(s) 100 may provide a secondary barrier to preventthe ingress contaminants that breach the seal between the flange 84 ofthe seal member 40 and the container contact region 72 of the container70. In embodiments including the annular rib(s) 100, the outer diameterD2 of the proximal end 81 of the seal member 40 may be equal to or lessthan inner diameter D1 of the container 15 while the rib(s) 100 can beslightly larger than D1 in diameter such that the rib(s) 100 compressupon assembly to ensure a tight seal. In other embodiments, the annularrib(s) 100 may be omitted (see FIGS. 3A and 3B), and the outer diameterD2 of the proximal end 81 of the seal member 40 may be slightly largerthan the inner diameter D1 of the container 15 to provide a tight fitand seal. In still further embodiments, the annular ribs 100 may beomitted and the outer diameter D2 of the proximal end 81 of the sealmember 40 may be smaller than the inner diameter D1 of the container 15,such that there is no seal formed therebetween.

Referring back to FIG. 2A, a depression or recess 80 may be formed inthe seal member 40 and dimensioned to receive the proximal end 65 of theovermold member 62. The recess 80 may start at the distal end surface 75of the seal member 40 and extend into the seal member 40 to a positionwhich is located in the distal direction relative to the proximal endsurface 73 of the seal member 40. Accordingly, the recess 80 may definea blind bore having a depth X1. The recess 80 may be defined by aninterior surface 79 of the seal member 40. In some embodiments, therecess 79 may receive the overmold member 62 via an interference-fitconnection (also referred to as a press-fit connection), such that theinterior surface 79 of the seal member 40 sealingly engages an exteriorsurface 77 of the overmold member 62 to prevent or inhibit the ingressof microbes and other contaminants. The interference-fit connection maybe achieved by constructing the proximal end 65 of the overmold member62 with an outer diameter D4 (or other outer dimension) that is largerthan or equal to the inner diameter D5 (or other inner dimension) of therecess 80. The interference-fit connection may result in frictionbetween the interior surface 79 of the seal member 40 and the exteriorsurface 77 of the overmold member 62 that resists movement of theovermold member 62 relative to the seal member 40. In other embodiments,the outer diameter D4 of the proximal end 65 of the overmold member 62may be smaller than the inner diameter D5 of the recess 80, and anO-ring (not illustrated) may be disposed around the proximal end 65 ofthe overmold member 62 to sealingly engage the interior surface 79 ofthe seal member 40 to prevent or inhibit the ingress of contaminants.

Referring to FIG. 2B, the enclosed clean space 68 may be formed byinserting the proximal end 65 of the overmold member 62 partially intothe recess 80, such that the proximal end 65 of the overmold member 62does not extend the entire depth X1 into the recess 80. The resultinggap between the proximal end 65 of the overmold member 62 and the bottomof the recess 80 may correspond to the enclosed clean space 68. In thisway, the enclosed clean space 68 may be defined within the recess 80.

FIG. 2B illustrates that at least a portion of the recess 80 may bedisposed in a proximal direction relative to the container contactregion 72 of the container 15. Accordingly, at least a portion of therecess 80 may be disposed within the container 15. Thus, when insertedinto the recess 80, at least a portion of the overmold member 62 mayalso be disposed within the container 15. This may reduce an axiallength of the overmold member 62 which is disposed exterior to thecontainer 15, which in turn may save space within the body 29 of thedrug delivery device 10. As a result, the drug delivery device 10 may bepermitted to have a more compact design.

The configuration shown in FIG. 2B corresponds to a storage position orstate of the container access needle 60 and the overmold member 62. Theovermold member 62 may be held statically in the storage position for aperiod of time between the completion of assembly of the drug deliverydevice 10 and activation of the drug delivery device 10 by a user orpatient. As shown in FIG. 2B, in the storage position, the point 63 ofthe container access needle 60 may be disposed in the enclosed cleanspace 68 and thus exterior to the reservoir 30. In other embodiments,when arranged in the storage position, the point 63 of the containeraccess needle 60 may be disposed partially through the seal member 40such that the point 63 is embedded within the material of the sealmember 40 but nonetheless disposed exterior to the reservoir 30, asdescribed above.

In order to prevent the tip 63 of the container access needle 60 fromprematurely piercing through the seal member 40 into the reservoir 30,the clip member 53 may frictionally engage the exterior surface 77 ofthe overmold member 62. In some embodiments, this may be accomplished byconstructing the clip member 53 with a gripping element 90 (see FIG. 2A)that is received in a corresponding groove 92 (see FIG. 2A) formed inthe exterior surface 77 of the overmold member 62 in the storage state,as shown in FIG. 2B. Friction between the gripping element 90 and thegroove 92 may advantageously resist movement of the overmold member 62,and thus the container access needle 60, toward and/or away from theseal member 40 prior to use of the drug delivery device 10. Uponactivation of the drug delivery device 10, an actuator (e.g., theactuator 28 or an internal energized actuator) may be configured toexert a motive force overcoming the frictional force between thegripping element 90 and the groove 92, and also any frictional forcebetween the overmold member 62 and the interior surface 79 of the sealmember 40 if an interference-fit connection exists therebetween, tocause the gripping element 90 to slide out of the groove 92 and move theovermold member 62 from the storage position (FIG. 2B) to the deliveryposition (FIG. 2C). As a result, the point 63 of the container accessneedle 60 may pierce through the proximal end surface 73 of the sealmember 40 into the reservoir 30, thereby establishing fluidcommunication with the drug 32.

In the present embodiment, the gripping element 90 may be configured asa continuous annular ridge or protrusion. In other embodiments,multiple, distinct gripping elements may be formed on the clip member53, each of which may be received in a corresponding groove formed inthe exterior surface 77 of the overmold member 62 in the storage state.

Referring back to FIG. 2A, the clip member 53 may have an interiorsurface 94 defining a through hole 95. The through hole 95 may extendbetween a proximal end surface 96 and a distal end surface 97 of theclip member 53. The proximal end surface 96 of the clip member 53 may bedisposed in direct contact with the distal end surface 75 of the sealmember 40. The overmold member 62 may extend entirely through thethrough hole 95 when assembled to the clip member 53, as illustrated inFIGS. 2B and 2C. The gripping element 90 may be disposed on or formed bythe interior surface 94, such that the gripping element 90 extendsradially inwardly into the through hole 95.

As illustrated in FIGS. 2B and 2C, the coupling device 91 may beconfigured to hold or clamp the clip member 53 to the container 15, withthe seal member 40 positioned between clip member 53 and the container15. In some embodiments, the coupling device 91 may take the form of acrimp ring that is applied to the container 15 and clip member 53 with acrimping tool. The coupling device 91 may further be adapted to apply aforce against the seal member 40 that causes it to compress towards thesecond end 37 of the container 15. As shown in FIGS. 2B and 2C, thecoupling device 91 may include radially inwardly extending flanges 93 aand 93 b that abut against, respectively, a proximally facing surface ofthe container flange 70 (or other exterior surface of the wall 38 of thecontainer 15) and the distal end surface 97 of the clip member 53, inorder to clamp or press the seal member contact region 74 of the flange84 of the seal member 40 tightly against the container contact region 72of the container 70. The clamping force provided by the fastener 94 mayhelp ensure an air-tight and/or fluid-tight seal at the sealinginterface 72 a between the seal member contact region 74 and thecontainer contact region 72.

Upon assembling the container assembly 14, the arrangement may besubjected to electron beam irradiation to sterilize any residualcontaminants trapped within the clean space 68 and/or the sealinginterface 72 a. As illustrated in FIGS. 4-6, an electron beam generator105 can be positioned above the container assembly 14 to generate asterilizing beam 106 to penetrate any or all of the seal member 40, thecoupling device 91, the overmold member 62, the clip member 53, and thesealing interface 72 a (formed by the seal member contact region 74 andthe container contact region 72).

In order to effectively sterilize the second end 37 of the containerassembly 14, it is necessary to determine an appropriate electron energylevel that will maximize penetration (or dosage) of the sterilizing beam106 at the sealing interface 72 a while approaching zero penetration forthe remainder of the elongated portion or wall 38 of the container 15 toensure the container 15 does not discolor (which would preventinspection) or otherwise chemically react in a way that may affect druginteraction or mechanical properties of the container 15. Based ondesired dimensions of the particular container assembly 14, electronbeams may be used having any energy level between approximately 0.3 MeVand approximately 5.0 MeV, or any energy level between approximately 0.5MeV and approximately 3 MeV, or any energy level between approximately 1MeV and approximately 2 MeV, or any energy level between approximately1.1 MeV and approximately 1.7 MeV, or any energy level equal toapproximately 1.5 MeV. These energy levels may result in a consistentdose to achieve the desired sterility assurance level (SAL) or couldsimply be to achieve a disinfection or other desired level of bioburdenreduction. Each aim, especially in conjunction with the typicalbioburden levels of the particular product, would result in a specificdesirable goal dose that could be anywhere from approximately 5 toapproximately 50 kGy, and in one version approximately 25 kGy, acrossthe flange site 70 or sealing interface 72 a. The goal dose may beachieved through a single exposure, as discussed, or it may be achievedin multiple lower exposures separated in time that cumulatively add upto the goal dose. For example, in some versions, even multiple sub-5 kGydoses could be applied over time to ultimately achieve the desired goaldose. Other examples are possible. In some approaches, some componentsof the container assembly 14 may be subject to prior sterilizationprocesses as desired. In order to achieve the desired SterilityAssurance Level (SAL) with a high reliability and confidence inaccordance with current good manufacturing practices, in-situ dosimetrywithin the container assembly 14 may be required during development,initial validation, and routine process validation. One such dosimetrytechnique would be to use commercially available NIST-traceable polymerdosimetry film. The film would be cut to a custom geometry that wouldpermit it to be placed into interface 72 a during the assembly ofcontainer assembly 14 in a manner that does not materially affect theposition and orientation of any other components in container assembly14. Thus assembled, such a container would now be a ‘dosimetercontainer’ that can be included in a larger batch sterilization process,disassembled after the process to extract the dosimeter film, and havethat dosimeter film measured to discern the dose delivered to thatcontainer. Using such a technique, routine process measurements can bemade and validations can be carried out to ensure that the desired SALwill be achieved.

As illustrated in FIGS. 5-7B, the container assembly 14 can be at leastpartially disposed in a receptacle 112 of a housing 110 of a shieldingmember that acts as a nest to shield certain aspects of the containerassembly 14 from the sterilizing beam 106. The housing 110 may includeone or a plurality of receptacles 112 to accommodate one or a pluralityof container assemblies 14. The housing 110 may be constructed of anynumber of materials generally having a low atomic number (i.e., low-Znumber). For example, the housing 110 may be constructed from aluminum,ceramics such as boron nitride, polymers such as polyethylene, ABS,polystyrene, or other polymers. Such materials can advantageouslyminimize production of x-rays created through Bremsstrahlung irradiationthat may penetrate further than the electrons and thus discolor orotherwise impact the container assembly 14.

As shown in FIGS. 5 and 6, the housing 110 in the depicted version isbifurcated into a first shielding portion 111 and a second shieldingportion 113 separated by an interface 115, which may be a physical orvirtual interface depending on the specific construct of the housing110, as will be discussed more below. The first shielding portion 111includes a first surface 111 a, a second surface 111 b opposite thefirst surface 111 a, and a first bore portion 112 a extendingtherebetween. The first bore portion 112 a defines an opening 117 in thefirst surface 111 a of the first shielding portion 111. The secondshielding portion 113 has a first surface 113 a, a second surface 113 bopposite the first surface 113 a, and a second bore portion 112 bextending therebetween. The first surface 113 a of the second shieldingportion 113 is adjacent to the second surface 111 b of the firstshielding portion 111 at the interface 115. So configured, the first andsecond bore portions 112 a, 112 b are aligned with each other to definethe complete receptacle 112. It should be appreciated that while FIGS. 5and 6 depict housings 110 with only a single receptacle 112, otherversions of the shielding member includes a plurality of receptacles112, each formed by complementary first and second bore portions 112 a,112 b.

In some examples, the second bore portion 112 b of the second shieldingportion 113 may extend completely between the first and second surfaces113 a, 113 b, thereby forming a bore that extends completely through thesecond shielding portion 113. But in other examples, the second boreportion 112 b may only extend partly through the second shieldingportion 113, i.e., through the first surface 113 a and into the secondshielding portion 113 but short of the second surface 113 b, therebydefining a blind bore or cup-shaped recess.

The first shielding portion 111 and the second shielding portion 113cooperate to define a number of blocking regions 114 positioned near thecontainer 15 and container assembly 14 to restrict the sterilizing beam106 from producing incidental, off-axis, angular, and/or reflected beamswhich may otherwise pass through the receptacle 112 and become incidenton the container assembly 14. For example, the housing 110 may include afirst blocking region 114 a positioned near the distal end 37 of thecontainer assembly 14. In the illustrated example, the first blockingregion 114 a may include a step portion 116 to accommodate the shoulder76 of the container 15, thereby allowing the container 15 to nest withinthe receptacle 112 and be properly located within the housing 110. Inother words, the receptacle 112 may include portions having varyingdiameters to accommodate specific dimensions of the container 15. In thedepicted version, for example, the first bore portion 112 a of thereceptacle has a diameter that is smaller than a diameter of the secondbore portion 112 b. In other versions, the first and second boreportions 112 a, 112 b can have the same diameters.

In some examples, the second end 38 of the container assembly 14 isexposed through the opening 117 in the housing 110 during thesterilization process, as depicted in FIG. 5. This configuration ensuresthat the sterilization beam 106 is incident on the second end 38 of thecontainer assembly 14 to provide the intended sterilization of thesealing interface 72 a and/or other components. Further, during thesterilization process, the first blocking region 114 a may retard orotherwise restrict irradiation from progressing towards the first end 36of the container 15 a distance beyond the shoulder 76. That is, the stepportion 116 may restrict or shield axial propagation (i.e., in adirection that is generally parallel to axis A) of the sterilizing beam106.

The housing 110 may further include a second blocking region 114 bpositioned near the elongated portion 38 of the container 15. The secondblocking region 114 b protects the wall 38 of the container 15 and thedrug 32 from unwanted exposure to the sterilizing beam 106. In someexamples, the first shielding portion 111 and the second shieldingportion 113 are integrally formed, and in some examples, the firstshielding portion 111 and the second shielding portion 113 are distinctparts separated at the interface 115, for example, and stacked togetherwithout coupling, or they may be coupled together via any number ofsuitable approaches such as, for example, hinges, fasteners, and/orclasping devices. Additionally, the first shielding portion 111 andsecond shielding portion 113 may each themselves be made of multiplecomponents that may be stacked or joined together.

In some forms, the blocking regions 114 may restrict propagation of thesterilizing beam 106 in any direction (i.e., in both a direction that isgenerally parallel to axis A and a direction that is non-orthogonal toaxis A). Specifically, the blocking regions 114 a, 114 b may restrictthe propagation of any sterilizing beams 106 that come into contact withthe housing 110 in any direction. As a result, the sterilizing beam 106may only be permitted to propagate through the container assembly 14,and any portions of the beam reflected, both directly and indirectly,into the housing 110 will be absorbed and not reflected. The housing 110is sufficiently thick and has sufficiently spaced holes 112 to absorbthe sterilizing beams 106.

By predetermining the energy of the sterilizing beam 106, thesterilizing beam 106 will only have sufficient energy to advance to adepth that is generally near the shoulder 76 of the container 15.Accordingly, the sterilizing beam 106 will make contact with any or allof the seal member 40, the coupling device 91, the overmold member 62,the clip member 53, and the sealing interface 72 a (formed by the sealmember contact region 74 and the container contact region 72). In oneembodiment, the sterilizing beam 106 may have a dose of approximately 25kGy at the sealing interface 72 a.

The container assembly 14, the housing 110, and the electron beamgenerator 105 may have any number of configurations. For example, asillustrated in the alternative embodiment presented in FIG. 6, theshoulder 76 may be pronounced due to the use of a flange 70 that issubstantially narrower than the remainder of the container 15. In thisembodiment, the housing 110 includes a first receptacle 112 a having afirst diameter and a second receptacle 112 b having a second diameterthat is substantially greater than the first diameter. However, in someembodiments (not shown), the receptacle 112 may have a constant diameterthroughout its entire length.

In still other embodiments, the housing can be constructed to have aside-shielding portion. For example, FIGS. 8 and 9 depict onealternative housing 210 used in conjunction with a storage tub 201 forcontaining a plurality of container assemblies 14. The housing 210 inthe depicted version includes a pair of stacked plates 203 a, 203 b, butcould include a single plate or more than a pair of plates. The housing210 includes a first shielding portion 211 and a second shieldingportion 213. The first shielding portion 211 includes generally flatplate portion with a first surface 211 a, a second surface 211 bopposite the first surface 211 a, and a plurality of bores 212 aextending therebetween. Each bore 212 a defines an opening 217 in thefirst surface 211 a of the first shielding portion 211. The secondshielding portion 213 extends from a perimeter of the first shieldingportion 211 downward at an angle α relative to horizontal. Soconfigured, the second shielding portion 213 acts as a side-shieldingmember when the assembly is loaded into the tub 201 as shown in FIG. 9.Specifically, as shown, a plurality of container assemblies 14 can beloaded in to the tub 201 in the upright standing orientation.Subsequently, the housing 201 can be placed into the tub 201 such thatthe plurality of bores 212 a receive the container assemblies 14 therebyaligning the first shielding portion 211 above the container assemblies14 to protect the container assemblies 14 from downward projectedsterilizing radiation. Additionally, as can be seen in FIG. 9, a distalend 215 of the second shielding portion 213 engages and rests upon ashelf surface 203 of the tub 201, which supports the housing 210 in thetub 201 and maintains the alignment of the housing 210 relative to thecontainer assemblies 14. Moreover, as mentioned, the second shieldingportion 213 serves as a side shielding member to prevent radiation thatmay other reflect inside of the tub 201 and impinge upon the containerassemblies 14 from the perimeter region of the tub 201.

FIGS. 10 and 11 show another alternative embodiment of a housing 310similar to that of FIGS. 8 and 9. In FIGS. 10 and 11, housing 310 isalso used in conjunction with a storage tub 301 for containing aplurality of container assemblies 14. The housing 310 in the depictedversion includes a single piece construction, but could include multiplepieces. The housing 310 includes a first shielding portion 311 and asecond shielding portion 313. The first shielding portion 311 includesgenerally flat plate portion with a first surface 311 a, a secondsurface 311 b opposite the first surface 311 a, and a plurality of bores312 a extending therebetween. Each bore 312 a defines an opening 317 inthe first surface 311 a of the first shielding portion 311. The secondshielding portion 313 extends from a perimeter of the first shieldingportion 311 downward. So configured, the second shielding portion 313acts as a side-shielding member when the assembly is loaded into the tub301 as shown in FIG. 11. Specifically, as shown, a plurality ofcontainer assemblies 14 can be loaded in to the tub 301 in the uprightstanding orientation. Subsequently, the housing 301 can be placed intothe tub 301 such that the plurality of bores 312 a receive the containerassemblies 14 thereby aligning the first shielding portion 311 above thecontainer assemblies 14 to protect the container assemblies 14 fromdownward projected sterilizing radiation. Additionally, as can be seenin FIG. 11, a distal end 315 of the second shielding portion 313 engagesand rests upon a shelf surface 303 of the tub 301, which supports thehousing 310 in the tub 301 and maintains the alignment of the housing310 relative to the container assemblies 14. Moreover, as mentioned, thesecond shielding portion 313 serves as a side shielding member toprevent radiation that may other reflect inside of the tub 301 andimpinge upon the container assemblies 14 from the perimeter region ofthe tub 301. Unlike the housing in FIGS. 8 and 9, the second shieldingportion 313 of the housing 310 in FIGS. 10 and 11 extends generallyperpendicularly downward from horizontal and stands on the shelf surface303 of the tub 301. But in other versions, the second shielding portion313 could extend at an angle relative to horizontal. Another distinctionis that the housing 301 in FIGS. 10 and 11 includes added side shieldingprotection for the individual container assemblies. That is, as can beseen in FIGS. 10 and 11, the housing 310 includes a plurality ofcylindrical collars 319 a and 319 b extending down from the secondsurface 311 b of the first shielding portion 311 for receiving thecontainer assemblies 14. Interior surfaces 323 of the collards 319 canbe contoured to closely fit and receive the container assemblies 14.Collars 319 a are located around the perimeter of the housing 310, andcollars 319 b are located interior. The perimeter collars 319 a arelonger and cover more of the respective container assemblies 14. Thatis, distal ends 321 of the perimeter collars 319 a can engage and restupon the shelf surface 303 of the tub 301 same as the distal ends 315 ofthe second shielding portion 313. So configured, the collars 319 providean extra added layer of protection against the possibility of radiationpenetrating the housing 310 from the side perimeter of the tub 301 orotherwise.

Those skilled in the art will recognize that a wide variety ofmodifications, alterations, and combinations can be made with respect tothe above described embodiments without departing from the scope of theinvention, and that such modifications, alterations, and combinationsare to be viewed as being within the ambit of the inventive concept. Forexample, the container assembly 14 of the foregoing description andclaims tends to resemble a cartridge for use in drug delivery devices,the disclosure is not limited in this regard. In other versions, thecontainer assembly 14 can include a conventional vial or syringe barrel,for example, as such containers would also benefit from the teachingspresented. Additionally, the means of sterilizing radiation may beselected to be principally from photons (i.e. x-rays) rather thanelectrons or some combination of photons and electrons. In this case,the generator 105 may be oriented similarly but have other means ofgenerating ionizing radiation. An x-ray source may come from anelectron-beam generator, or by other means. In the case where theionizing radiation is principally x-rays, the appropriate photon (x-ray)energy level ranges will be different than those described forelectrons, since photons will penetrate further through materials thanelectrons of the same energy level. Based on desired dimensions of theparticular container assembly 14, x-ray beams may be used having anyenergy level between approximately 3 keV and approximately 50 keV, orany energy level between approximately 5 keV and approximately 25 keV,or any energy level between approximately 8 keV and approximately 20keV.

Drug Information

As mentioned above, the container of the drug delivery device may befilled with a drug. This drug may be any one or combination of the drugslisted below, with the caveat that the following list should neither beconsidered to be all inclusive nor limiting.

For example, the container may be filled with colony stimulatingfactors, such as granulocyte colony-stimulating factor (G-CSF). SuchG-CSF agents include, but are not limited to, Neupogen® (filgrastim) andNeulasta® (pegfilgrastim). In various other embodiments, the containermay be used with various pharmaceutical products, such as anerythropoiesis stimulating agent (ESA), which may be in a liquid or alyophilized form. An ESA is any molecule that stimulates erythropoiesis,such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo®(epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta),Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon®(epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa),epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta),Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa,epoetin beta, epoetin zeta, epoetin theta, and epoetin delta, as well asthe molecules or variants or analogs thereof as disclosed in thefollowing patents or patent applications, each of which is hereinincorporated by reference in its entirety: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,986,047; 6,583,272; 7,084,245; and 7,271,689;and PCT Publication Nos. WO 91/05867; WO 95/05465; WO 96/40772; WO00/24893; WO 01/81405; and WO 2007/136752.

An ESA can be an erythropoiesis stimulating protein. As used herein,“erythropoiesis stimulating protein” means any protein that directly orindirectly causes activation of the erythropoietin receptor, forexample, by binding to and causing dimerization of the receptor.Erythropoiesis stimulating proteins include erythropoietin and variants,analogs, or derivatives thereof that bind to and activate erythropoietinreceptor; antibodies that bind to erythropoietin receptor and activatethe receptor; or peptides that bind to and activate erythropoietinreceptor. Erythropoiesis stimulating proteins include, but are notlimited to, epoetin alfa, epoetin beta, epoetin delta, epoetin omega,epoetin iota, epoetin zeta, and analogs thereof, pegylatederythropoietin, carbamylated erythropoietin, mimetic peptides (includingEMP1/hematide), and mimetic antibodies. Exemplary erythropoiesisstimulating proteins include erythropoietin, darbepoetin, erythropoietinagonist variants, and peptides or antibodies that bind and activateerythropoietin receptor (and include compounds reported in U.S.Publication Nos. 2003/0215444 and 2006/0040858, the disclosures of eachof which is incorporated herein by reference in its entirety) as well aserythropoietin molecules or variants or analogs thereof as disclosed inthe following patents or patent applications, which are each hereinincorporated by reference in its entirety: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,830,851; 5,856,298; 5,986,047; 6,030,086;6,310,078; 6,391,633; 6,583,272; 6,586,398; 6,900,292; 6,750,369;7,030,226; 7,084,245; and 7,217,689; U.S. Publication Nos. 2002/0155998;2003/0077753; 2003/0082749; 2003/0143202; 2004/0009902; 2004/0071694;2004/0091961; 2004/0143857; 2004/0157293; 2004/0175379; 2004/0175824;2004/0229318; 2004/0248815; 2004/0266690; 2005/0019914; 2005/0026834;2005/0096461; 2005/0107297; 2005/0107591; 2005/0124045; 2005/0124564;2005/0137329; 2005/0142642; 2005/0143292; 2005/0153879; 2005/0158822;2005/0158832; 2005/0170457; 2005/0181359; 2005/0181482; 2005/0192211;2005/0202538; 2005/0227289; 2005/0244409; 2006/0088906; and2006/0111279; and PCT Publication Nos. WO 91/05867; WO 95/05465; WO99/66054; WO 00/24893; WO 01/81405; WO 00/61637; WO 01/36489; WO02/014356; WO 02/19963; WO 02/20034; WO 02/49673; WO 02/085940; WO03/029291; WO 2003/055526; WO 2003/084477; WO 2003/094858; WO2004/002417; WO 2004/002424; WO 2004/009627; WO 2004/024761; WO2004/033651; WO 2004/035603; WO 2004/043382; WO 2004/101600; WO2004/101606; WO 2004/101611; WO 2004/106373; WO 2004/018667; WO2005/001025; WO 2005/001136; WO 2005/021579; WO 2005/025606; WO2005/032460; WO 2005/051327; WO 2005/063808; WO 2005/063809; WO2005/070451; WO 2005/081687; WO 2005/084711; WO 2005/103076; WO2005/100403; WO 2005/092369; WO 2006/50959; WO 2006/02646; and WO2006/29094.

Examples of other pharmaceutical products for use with the device mayinclude, but are not limited to, antibodies such as Vectibix®(panitumumab), Xgeva™ (denosumab) and Prolia™ (denosamab); otherbiological agents such as Enbrel® (etanercept, TNF-receptor/Fc fusionprotein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF,hu-MetG-CSF), and Nplate® (romiplostim); small molecule drugs such asSensipar® (cinacalcet). The device may also be used with a therapeuticantibody, a polypeptide, a protein or other chemical, such as an iron,for example, ferumoxytol, iron dextrans, ferric glyconate, and ironsucrose. The pharmaceutical product may be in liquid form, orreconstituted from lyophilized form.

Among particular illustrative proteins are the specific proteins setforth below, including fusions, fragments, analogs, variants orderivatives thereof:

OPGL specific antibodies, peptibodies, and related proteins, and thelike (also referred to as RANKL specific antibodies, peptibodies and thelike), including fully humanized and human OPGL specific antibodies,particularly fully humanized monoclonal antibodies, including but notlimited to the antibodies described in PCT Publication No. WO 03/002713,which is incorporated herein in its entirety as to OPGL specificantibodies and antibody related proteins, particularly those having thesequences set forth therein, particularly, but not limited to, thosedenoted therein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, including theOPGL specific antibodies having either the light chain of sequenceidentification number:2 as set forth therein in FIG. 2 and/or the heavychain of sequence identification number:4, as set forth therein in FIG.4, each of which is individually and specifically incorporated byreference herein in its entirety fully as disclosed in the foregoingpublication;

Myostatin binding proteins, peptibodies, and related proteins, and thelike, including myostatin specific peptibodies, particularly thosedescribed in U.S. Publication No. 2004/0181033 and PCT Publication No.WO 2004/058988, which are incorporated by reference herein in theirentirety particularly in parts pertinent to myostatin specificpeptibodies, including but not limited to peptibodies of the mTN8-19family, including those of sequence identification number:305-351,including TN8-19-1 through TN8-19-40, TN8-19 con1 and TN8-19 con2;peptibodies of the mL2 family of sequence identificationnumbers:357-383; the mL15 family of sequence identificationnumbers:384-409; the mL17 family of sequence identificationnumbers:410-438; the mL20 family of sequence identificationnumbers:439-446; the mL21 family of sequence identificationnumbers:447-452; the mL24 family of sequence identificationnumbers:453-454; and those of sequence identification numbers:615-631,each of which is individually and specifically incorporated by referenceherein in their entirety fully as disclosed in the foregoingpublication;

IL-4 receptor specific antibodies, peptibodies, and related proteins,and the like, particularly those that inhibit activities mediated bybinding of IL-4 and/or IL-13 to the receptor, including those describedin PCT Publication No. WO 2005/047331 or PCT Application No.PCT/US2004/37242 and in U.S. Publication No. 2005/112694, which areincorporated herein by reference in their entirety particularly in partspertinent to IL-4 receptor specific antibodies, particularly suchantibodies as are described therein, particularly, and withoutlimitation, those designated therein: L1H1; L1H2; L1H3; L1H4; L1H5;L1H6; L1H7; L1H8; L1H9; L1H10; L1H11; L2H1; L2H2; L2H3; L2H4; L2H5;L2H6; L2H7; L2H8; L2H9; L2H10; L2H11; L2H12; L2H13; L2H14; L3H1; L4H1;L5H1; L6H1, each of which is individually and specifically incorporatedby reference herein in its entirety fully as disclosed in the foregoingpublication;

Interleukin 1-receptor 1 (“IL1-R1”) specific antibodies, peptibodies,and related proteins, and the like, including but not limited to thosedescribed in U.S. Publication No. 2004/097712, which is incorporatedherein by reference in its entirety in parts pertinent to IL1-R1specific binding proteins, monoclonal antibodies in particular,especially, without limitation, those designated therein: 15CA, 26F5,27F2, 24E12, and 10H7, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe aforementioned publication;

Ang2 specific antibodies, peptibodies, and related proteins, and thelike, including but not limited to those described in PCT PublicationNo. WO 03/057134 and U.S. Publication No. 2003/0229023, each of which isincorporated herein by reference in its entirety particularly in partspertinent to Ang2 specific antibodies and peptibodies and the like,especially those of sequences described therein and including but notlimited to: L1(N); L1(N) WT; L1(N) 1K WT; 2xL1(N); 2xL1(N) WT; Con4 (N),Con4 (N) 1K WT, 2xCon4 (N) 1K; L1C; L1C 1K; 2xL1C; Con4C; Con4C 1K;2xCon4C 1K; Con4-L1 (N); Con4-L1C; TN-12-9 (N); C17 (N); TN8-8(N);TN8-14 (N); Con 1 (N), also including anti-Ang 2 antibodies andformulations such as those described in PCT Publication No. WO2003/030833 which is incorporated herein by reference in its entirety asto the same, particularly Ab526; Ab528; Ab531; Ab533; Ab535; Ab536;Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558;Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12;AblA1; AbIF; Abl K, AbIP; and AbIP, in their various permutations asdescribed therein, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing publication;

NGF specific antibodies, peptibodies, and related proteins, and the likeincluding, in particular, but not limited to those described in U.S.Publication No. 2005/0074821 and U.S. Pat. No. 6,919,426, which areincorporated herein by reference in their entirety particularly as toNGF-specific antibodies and related proteins in this regard, includingin particular, but not limited to, the NGF-specific antibodies thereindesignated 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11, each of which isindividually and specifically incorporated by reference herein in itsentirety fully as disclosed in the foregoing publication;

CD22 specific antibodies, peptibodies, and related proteins, and thelike, such as those described in U.S. Pat. No. 5,789,554, which isincorporated herein by reference in its entirety as to CD22 specificantibodies and related proteins, particularly human CD22 specificantibodies, such as but not limited to humanized and fully humanantibodies, including but not limited to humanized and fully humanmonoclonal antibodies, particularly including but not limited to humanCD22 specific IgG antibodies, such as, for instance, a dimer of ahuman-mouse monoclonal hLL2 gamma-chain disulfide linked to ahuman-mouse monoclonal hLL2 kappa-chain, including, but limited to, forexample, the human CD22 specific fully humanized antibody inEpratuzumab, CAS registry number 501423-23-0;

IGF-1 receptor specific antibodies, peptibodies, and related proteins,and the like, such as those described in PCT Publication No. WO06/069202, which is incorporated herein by reference in its entirety asto IGF-1 receptor specific antibodies and related proteins, includingbut not limited to the IGF-1 specific antibodies therein designatedL1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11,L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20,L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29,L30H30, L31H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38,L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47,L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1R-binding fragments andderivatives thereof, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing publication;

Also among non-limiting examples of anti-IGF-1R antibodies for use inthe methods and compositions of the present disclosure are each and allof those described in:

(i) U.S. Publication No. 2006/0040358 (published Feb. 23, 2006),2005/0008642 (published Jan. 13, 2005), 2004/0228859 (published Nov. 18,2004), including but not limited to, for instance, antibody 1A (DSMZDeposit No. DSM ACC 2586), antibody 8 (DSMZ Deposit No. DSM ACC 2589),antibody 23 (DSMZ Deposit No. DSM ACC 2588) and antibody 18 as describedtherein;

(ii) PCT Publication No. WO 06/138729 (published Dec. 28, 2006) and WO05/016970 (published Feb. 24, 2005), and Lu et al. (2004), J. Biol.Chem. 279:2856-2865, including but not limited to antibodies 2F8, A12,and IMC-A12 as described therein;

(iii) PCT Publication No. WO 07/012614 (published Feb. 1, 2007), WO07/000328 (published Jan. 4, 2007), WO 06/013472 (published Feb. 9,2006), WO 05/058967 (published Jun. 30, 2005), and WO 03/059951(published Jul. 24, 2003);

(iv) U.S. Publication No. 2005/0084906 (published Apr. 21, 2005),including but not limited to antibody 7C10, chimaeric antibody C7C10,antibody h7C10, antibody 7H2M, chimaeric antibody *7C10, antibody GM607, humanized antibody 7C10 version 1, humanized antibody 7C10 version2, humanized antibody 7C10 version 3, and antibody 7H2HM, as describedtherein;

(v) U.S. Publication Nos. 2005/0249728 (published Nov. 10, 2005),2005/0186203 (published Aug. 25, 2005), 2004/0265307 (published Dec. 30,2004), and 2003/0235582 (published Dec. 25, 2003) and Maloney et al.(2003), Cancer Res. 63:5073-5083, including but not limited to antibodyEM164, resurfaced EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1,huEM164 v1.2, and huEM164 v1.3 as described therein;

(vi) U.S. Pat. No. 7,037,498 (issued May 2, 2006), U.S. Publication Nos.2005/0244408 (published Nov. 30, 2005) and 2004/0086503 (published May6, 2004), and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073,e.g., antibody CP-751,871, including but not limited to each of theantibodies produced by the hybridomas having the ATCC accession numbersPTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, andantibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3, asdescribed therein;

(vii) U.S. Publication Nos. 2005/0136063 (published Jun. 23, 2005) and2004/0018191 (published Jan. 29, 2004), including but not limited toantibody 19D12 and an antibody comprising a heavy chain encoded by apolynucleotide in plasmid 15H12/19D12 HCA (y4), deposited at the ATCCunder number PTA-5214, and a light chain encoded by a polynucleotide inplasmid 15H12/19D12 LCF (K), deposited at the ATCC under numberPTA-5220, as described therein; and

(viii) U.S. Publication No. 2004/0202655 (published Oct. 14, 2004),including but not limited to antibodies PINT-6A1, PINT-7A2, PINT-7A4,PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3,PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2,PINT-12A3, PINT-12A4, and PINT-12A5, as described therein; each and allof which are herein incorporated by reference in their entireties,particularly as to the aforementioned antibodies, peptibodies, andrelated proteins and the like that target IGF-1 receptors;

B-7 related protein 1 specific antibodies, peptibodies, related proteinsand the like (“B7RP-1,” also is referred to in the literature as B7H2,ICOSL, B7h, and CD275), particularly B7RP-specific fully humanmonoclonal IgG2 antibodies, particularly fully human IgG2 monoclonalantibody that binds an epitope in the first immunoglobulin-like domainof B7RP-1, especially those that inhibit the interaction of B7RP-1 withits natural receptor, ICOS, on activated T cells in particular,especially, in all of the foregoing regards, those disclosed in U.S.Publication No. 2008/0166352 and PCT Publication No. WO 07/011941, whichare incorporated herein by reference in their entireties as to suchantibodies and related proteins, including but not limited to antibodiesdesignated therein as follow: 16H (having light chain variable and heavychain variable sequences sequence identification number:1 and sequenceidentification number:7 respectively therein); 5D (having light chainvariable and heavy chain variable sequences sequence identificationnumber:2 and sequence identification number:9 respectively therein); 2H(having light chain variable and heavy chain variable sequences sequenceidentification number:3 and sequence identification number:10respectively therein); 43H (having light chain variable and heavy chainvariable sequences sequence identification number 6 and sequenceidentification number:14 respectively therein); 41H (having light chainvariable and heavy chain variable sequences sequence identificationnumber:5 and sequence identification number:13 respectively therein);and 15H (having light chain variable and heavy chain variable sequencessequence identification number:4 and sequence identification number:12respectively therein), each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing publication;

IL-15 specific antibodies, peptibodies, and related proteins, and thelike, such as, in particular, humanized monoclonal antibodies,particularly antibodies such as those disclosed in U.S. Publication Nos.2003/0138421; 2003/023586; and 2004/0071702; and U.S. Pat. No.7,153,507, each of which is incorporated herein by reference in itsentirety as to IL-15 specific antibodies and related proteins, includingpeptibodies, including particularly, for instance, but not limited to,HuMax IL-15 antibodies and related proteins, such as, for instance,146B7;

IFN gamma specific antibodies, peptibodies, and related proteins and thelike, especially human IFN gamma specific antibodies, particularly fullyhuman anti-IFN gamma antibodies, such as, for instance, those describedin U.S. Publication No. 2005/0004353, which is incorporated herein byreference in its entirety as to IFN gamma specific antibodies,particularly, for example, the antibodies therein designated 1118;1118*; 1119; 1121; and 1121*. The entire sequences of the heavy andlight chains of each of these antibodies, as well as the sequences oftheir heavy and light chain variable regions and complementaritydetermining regions, are each individually and specifically incorporatedby reference herein in its entirety fully as disclosed in the foregoingpublication and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115. Inaddition, description of the properties of these antibodies provided inthe foregoing publication is also incorporated by reference herein inits entirety. Specific antibodies include those having the heavy chainof sequence identification number:17 and the light chain of sequenceidentification number:18; those having the heavy chain variable regionof sequence identification number:6 and the light chain variable regionof sequence identification number:8; those having the heavy chain ofsequence identification number:19 and the light chain of sequenceidentification number:20; those having the heavy chain variable regionof sequence identification number:10 and the light chain variable regionof sequence identification number:12; those having the heavy chain ofsequence identification number:32 and the light chain of sequenceidentification number:20; those having the heavy chain variable regionof sequence identification number:30 and the light chain variable regionof sequence identification number:12; those having the heavy chainsequence of sequence identification number:21 and the light chainsequence of sequence identification number:22; those having the heavychain variable region of sequence identification number:14 and the lightchain variable region of sequence identification number:16; those havingthe heavy chain of sequence identification number:21 and the light chainof sequence identification number:33; and those having the heavy chainvariable region of sequence identification number:14 and the light chainvariable region of sequence identification number:31, as disclosed inthe foregoing publication. A specific antibody contemplated is antibody1119 as disclosed in the foregoing U.S. publication and having acomplete heavy chain of sequence identification number:17 as disclosedtherein and having a complete light chain of sequence identificationnumber:18 as disclosed therein;

TALL-1 specific antibodies, peptibodies, and the related proteins, andthe like, and other TALL specific binding proteins, such as thosedescribed in U.S. Publication Nos. 2003/0195156 and 2006/0135431, eachof which is incorporated herein by reference in its entirety as toTALL-1 binding proteins, particularly the molecules of Tables 4 and 5B,each of which is individually and specifically incorporated by referenceherein in its entirety fully as disclosed in the foregoing publications;

Parathyroid hormone (“PTH”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,756,480, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind PTH;

Thrombopoietin receptor (“TPO-R”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,835,809, which is herein incorporated by reference in its entirety,particularly in parts pertinent to proteins that bind TPO-R;

Hepatocyte growth factor (“HGF”) specific antibodies, peptibodies, andrelated proteins, and the like, including those that target theHGF/SF:cMet axis (HGF/SF:c-Met), such as the fully human monoclonalantibodies that neutralize hepatocyte growth factor/scatter (HGF/SF)described in U.S. Publication No. 2005/0118643 and PCT Publication No.WO 2005/017107, huL2G7 described in U.S. Pat. No. 7,220,410 and OA-5d5described in U.S. Pat. Nos. 5,686,292 and 6,468,529 and in PCTPublication No. WO 96/38557, each of which is incorporated herein byreference in its entirety, particularly in parts pertinent to proteinsthat bind HGF;

TRAIL-R2 specific antibodies, peptibodies, related proteins and thelike, such as those described in U.S. Pat. No. 7,521,048, which isherein incorporated by reference in its entirety, particularly in partspertinent to proteins that bind TRAIL-R2;

Activin A specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. PublicationNo. 2009/0234106, which is herein incorporated by reference in itsentirety, particularly in parts pertinent to proteins that bind ActivinA;

TGF-beta specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. Pat. No.6,803,453 and U.S. Publication No. 2007/0110747, each of which is hereinincorporated by reference in its entirety, particularly in partspertinent to proteins that bind TGF-beta;

Amyloid-beta protein specific antibodies, peptibodies, related proteins,and the like, including but not limited to those described in PCTPublication No. WO 2006/081171, which is herein incorporated byreference in its entirety, particularly in parts pertinent to proteinsthat bind amyloid-beta proteins. One antibody contemplated is anantibody having a heavy chain variable region comprising sequenceidentification number:8 and a light chain variable region havingsequence identification number:6 as disclosed in the foregoingpublication;

c-Kit specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. Publication No.2007/0253951, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind c-Kit and/or otherstem cell factor receptors;

OX40L specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. Publication No.2006/0002929, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind OX40L and/or otherligands of the OX40 receptor; and

Other exemplary proteins, including Activase® (alteplase, tPA); Aranesp®(darbepoetin alfa); Epogen® (epoetin alfa, or erythropoietin); GLP-1,Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonalantibody); Betaseron® (interferon-beta); Campath® (alemtuzumab,anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade®(bortezomib); MLN0002 (anti-a4ß7 mAb); MLN1202 (anti-CCR2 chemokinereceptor mAb); Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNFblocker); Eprex® (epoetin alfa); Erbitux® (cetuximab,anti-EGFR/HER1/c-ErbB-1); Genotropin® (somatropin, Human GrowthHormone); Herceptin® (trastuzumab, anti-HER2/neu (erbB2) receptor mAb);Humatrope® (somatropin, Human Growth Hormone); Humira® (adalimumab);insulin in solution; Infergen® (interferon alfacon-1); Natrecor®(nesiritide; recombinant human B-type natriuretic peptide (hBNP);Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide®(epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab,anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin);Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris™(eculizumab); pexelizumab (anti-05 complement); Numax® (MEDI-524);Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio®(lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4);Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (visilizumab); cantuzumabmertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega®(oprelvekin, human interleukin-11); Neulasta® (pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF); Neupogen® (filgrastim, G-CSF,hu-MetG-CSF); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonalantibody); Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNFαmonoclonal antibody); Reopro® (abciximab, anti-GP Ilb/Ilia receptormonoclonal antibody); Actemra® (anti-IL6 Receptor mAb); Avastin®(bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2a); Simulect®(basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO(anti-IL15 antibody, see U.S. Pat. No. 7,153,507); Tysabri®(natalizumab, anti-α4integrin mAb); Valortim® (MDX-1303, anti-B.anthracis protective antigen mAb); ABthrax™; Vectibix® (panitumumab);Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-1 trap (the Fc portionof human IgG1 and the extracellular domains of both IL-1 receptorcomponents (the Type I receptor and receptor accessory protein)); VEGFtrap (Ig domains of VEGFR1 fused to IgG1 Fc); Zenapax® (daclizumab);Zenapax® (daclizumab, anti-IL-2Ra mAb); Zevalin® (ibritumomab tiuxetan);Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonalantibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3/huFcfusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFαmAb); HGS-ETR1 (mapatumumab; human anti-TRAIL Receptor-1 mAb);HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab);M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab,anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C. difficileToxin A and Toxin B C mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC);anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333(anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-CriptomAb; anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-3019);anti-CTLA4 mAb; anti-eotaxin1 mAb (CAT-213); anti-FGF8 mAb;anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; anti-GDF-8 human mAb(MY0-029); anti-GM-CSF Receptor mAb (CAM-3001); anti-HepC mAb (HuMaxHepC); anti-IFNα mAb (MEDI-545, MDX-1103); anti-IGF1R mAb; anti-IGF-1RmAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12/1L23 mAb (CNTO1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5Receptor mAb; anti-integrin receptors mAb (MDX-018, CNTO 95); anti-IP10Ulcerative Colitis mAb (MDX-1100); anti-LLY antibody; BMS-66513;anti-Mannose Receptor/hCGβ mAb (MDX-1307); anti-mesothelin dsFv-PE38conjugate (CAT-5001); anti-PD1mAb (MDX-1106 (ONO-4538)); anti-PDGFRaantibody (IMC-3G3); anti-TGFß mAb (GC-1008); anti-TRAIL Receptor-2 humanmAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR/Flt-1 mAb; anti-ZP3 mAb(HuMax-ZP3); NVS Antibody #1; and NVS Antibody #2.

Also included can be a sclerostin antibody, such as but not limited toromosozumab, blosozumab, or BPS 804 (Novartis). Further included can betherapeutics such as rilotumumab, bixalomer, trebananib, ganitumab,conatumumab, motesanib diphosphate, brodalumab, vidupiprant,panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA. Additionally,included in the device can be a monoclonal antibody (IgG) that bindshuman Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9). Such PCSK9specific antibodies include, but are not limited to, Repatha®(evolocumab) and Praluent® (alirocumab), as well as molecules, variants,analogs or derivatives thereof as disclosed in the following patents orpatent applications, each of which is herein incorporated by referencein its entirety for all purposes: U.S. Pat. Nos. 8,030,547, 8,563,698,8,829,165, 8,859,741, 8,871,913, 8,871,914, 8,883,983, 8,889,834,8,981,064, 9,056,915, 8,168,762, 9,045,547, 8,030,457, 8,030,457,8,829,165, 8,981,064, 8,030,457, U.S. Publication No. 2013/0064825, U.S.Patent Application Publication No. 2012/0093818, U.S. Patent ApplicationPublication No. 2013/0079502, U.S. Patent Application Publication No.2014/0357850, U.S. Patent Application Publication No. 2011/0027287, U.S.Patent Application Publication No. 2014/0357851, U.S. Patent ApplicationPublication No. 2014/0357854, U.S. Patent Application Publication No.2015/0031870, U.S. Patent Application Publication No. 2013/0085265, U.S.Patent Application Publication No. 2013/0079501, U.S. Patent ApplicationPublication No. 2012/0213797, U.S. Patent Application Publication No.2012/0251544, U.S. Patent Application Publication No. 2013/0072665, U.S.Patent Application Publication No. 2013/0058944, U.S. Patent ApplicationPublication No. 2013/0052201, U.S. Patent Application Publication No.2012/0027765, U.S. Patent Application Publication No. 2015/0087819, U.S.Patent Application Publication No. 2011/0117011, U.S. Patent ApplicationPublication No. 2015/0004174, U.S. Provisional Patent Application No.60/957,668, U.S. Provisional Patent Application No. 61/008,965, U.S.Provisional Patent Application No. 61/010,630, U.S. Provisional PatentApplication No. 61/086,133, U.S. Provisional Patent Application No.61/125,304, U.S. Provisional Patent Application No. 61/798,970, U.S.Provisional Patent Application No. 61/841,039, U.S. Provisional PatentApplication No. 62/002,623, U.S. Provisional Patent Application No.62/024,399, U.S. Provisional Patent Application No. 62/019,729, U.S.Provisional Patent Application No. 62/067,637, U.S. patent applicationSer. No. 14/777,371, International Patent Application No.PCT/US2013/048714, International Patent Application No.PCT/US2015/040211, International Patent Application No.PCT/US2015/056972, International Patent Application Publication No.WO/2008/057457, International Patent Application Publication No.WO/2008/057458, International Patent Application Publication No.WO/2008/057459, International Patent Application Publication No.WO/2008/063382, International Patent Application Publication No.WO/2008/133647, International Patent Application Publication No.WO/2009/100297, International Patent Application Publication No.WO/2009/100318, International Patent Application Publication No.WO/2011/037791, International Patent Application Publication No.WO/2011/053759, International Patent Application Publication No.WO/2011/053783, International Patent Application Publication No.WO/2008/125623, International Patent Application Publication No.WO/2011/072263, International Patent Application Publication No.WO/2009/055783, International Patent Application Publication No.WO/2012/0544438, International Patent Application Publication No.WO/2010/029513, International Patent Application Publication No.WO/2011/111007, International Patent Application Publication No.WO/2010/077854, International Patent Application Publication No.WO/2012/088313, International Patent Application Publication No.WO/2012/101251, International Patent Application Publication No.WO/2012/101252, International Patent Application Publication No.WO/2012/101253, International Patent Application Publication No.WO/2012/109530, and International Patent Application Publication No.WO/2001/031007, International Patent Application Publication No.WO/2009/026558, International Patent Application Publication No.WO/2009/131740, International Patent Application Publication No.WO/2013/166448, and International Patent Application Publication No.WO/2014/150983.

Also included can be talimogene laherparepvec or another oncolytic HSVfor the treatment of melanoma or other cancers. Examples of oncolyticHSV include, but are not limited to talimogene laherparepvec (U.S. Pat.Nos. 7,223,593 and 7,537,924); OncoVEXGALV/CD (U.S. Pat. No. 7,981,669);OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143);G207, 1716; NV1020; NV12023; NV1034 and NV1042 (Vargehes et al. (2002),Cancer Gene Ther., 9(12):967-978).

Also included are TIMPs. TIMPs are endogenous tissue inhibitors ofmetalloproteinases (TIMPs) and are important in many natural processes.TIMP-3 is expressed by various cells or and is present in theextracellular matrix; it inhibits all the major cartilage-degradingmetalloproteases, and may play a role in role in many degradativediseases of connective tissue, including rheumatoid arthritis andosteoarthritis, as well as in cancer and cardiovascular conditions. Theamino acid sequence of TIMP-3, and the nucleic acid sequence of a DNAthat encodes TIMP-3, are disclosed in U.S. Pat. No. 6,562,596, issuedMay 13, 2003, the disclosure of which is incorporated by referenceherein. Description of TIMP mutations can be found in U.S. PublicationNo. 2014/0274874 and PCT Publication No. WO 2014/152012.

Also included are antagonistic antibodies for human calcitoningene-related peptide (CGRP) receptor and bispecific antibody moleculethat target the CGRP receptor and other headache targets. Furtherinformation concerning these molecules can be found in PCT ApplicationNo. WO 2010/075238.

Additionally, a bispecific T cell engager antibody (BiTe), e.g.Blinotumomab can be used in the device. Alternatively, included can bean APJ large molecule agonist e.g., apelin or analogues thereof in thedevice. Information relating to such molecules can be found in PCTPublication No. WO 2014/099984.

In certain embodiments, the drug comprises a therapeutically effectiveamount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptorantibody. Examples of anti-TSLP antibodies that may be used in suchembodiments include, but are not limited to, those described in U.S.Pat. Nos. 7,982,016, and 8,232,372, and U.S. Publication No.2009/0186022. Examples of anti-TSLP receptor antibodies include, but arenot limited to, those described in U.S. Pat. No. 8,101,182. Inparticularly preferred embodiments, the drug comprises a therapeuticallyeffective amount of the anti-TSLP antibody designated as A5 within U.S.Pat. No. 7,982,016.

While the present disclosure has been described in connection withvarious embodiments, it will be understood that the present disclosureis capable of further modifications. The present disclosure is intendedto cover any variations, uses, or adaptations of the disclosed subjectmatter following, in general, the principles of the present disclosure,and including such departures from the present disclosure as, within theknown and customary practice within the art to which the presentdisclosure pertains.

It is noted that the construction and arrangement of the drug deliverydevice and its various components and assemblies as shown in the variousexemplary embodiments is illustrative only. Although only a fewembodiments of the subject matter at issue have been described in detailin the present disclosure, those skilled in the art who review thepresent disclosure will readily appreciate that many modifications arepossible (e.g., variations in sizes, dimensions, structures, shapes andproportions of the various elements, values of parameters, mountingarrangements, use of materials, colors, orientations, etc.) withoutmaterially departing from the novel teachings and advantages of thesubject matter disclosed herein. For example, elements shown asintegrally formed may be constructed of multiple parts or elements, andvice versa. Also, the position of elements may be reversed or otherwisevaried, and the nature or number of discrete elements or positions maybe altered or varied. Accordingly, all such modifications are intendedto be included within the scope of the present disclosure as defined inthe appended claims. Furthermore, the order or sequence of any processor method steps may be varied or re-sequenced according to alternativeembodiments. Other substitutions, modifications, changes and omissionsmay be made in the design, operating conditions and arrangement of thevarious exemplary embodiments without departing from the scope of thepresent disclosure.

What is claimed is:
 1. An on-body injector system comprising: a drugcontainer assembly including a container, a seal member, and a sealinginterface between the seal member and the container, the containerhaving an opening and the seal member at least partially covering theopening in the container; a fluid pathway assembly coupled to the drugcontainer assembly and including a needle, the needle being movablebetween a storage position, in which a point of the needle is spacedfrom the seal member, and a delivery position, in which the point of theneedle is disposed at least partially through the seal member; aradiation generator configured to emit rays of radiation to sterilizeand/or disinfect the sealing interface; a barrier disposed adjacent tothe sealing interface and having an opening; and wherein at least aportion of the drug container assembly is positioned adjacent to theopening in the barrier.
 2. The on-body injector system of claim 1,wherein the barrier includes a wall and the opening is formed in thewall.
 3. The on-body injector system of claim 2, wherein at least aportion of the container and the radiation source are disposed onopposite sides of the wall.
 4. The on-body injector system of claim 3,wherein the at least a portion of the seal member and the radiationsource are disposed on the same side of the wall.
 5. The on-bodyinjector system of claim 3, wherein the barrier includes a borecommunicating with the opening, and wherein the at least a portion ofthe seal member is disposed in the bore.
 6. The on-body injector systemof claim 5, wherein the at least a portion of the container is disposedoutside of the bore.
 7. The on-body injector system of claim 1, whereinthe opening in the container is coaxial with the opening in the barrier.8. The on-body injector system of claim 1, wherein the drug containerassembly includes a crimp ring coupling the seal member to thecontainer, at least a portion of the crimp ring extending through theopening in the barrier.
 9. The on-body injector system of claim 1,wherein the radiation generator a photon generator.
 10. The on-bodyinjector system of claim 9, wherein the radiation generator is anelectron beam generator.
 11. The on-body injector system of claim 1,wherein the barrier is a radiation shield.
 12. The on-body injectorsystem of claim 1, wherein the rays of radiation emitted by theradiation generator penetrate the seal member to sterilize or disinfectthe sealing interface between the seal member and the container.
 13. Theon-body injector system of claim 1, wherein the barrier limits exposureof at least a portion of the container to the rays of radiation emittedby the radiation generator during a sterilization or disinfectionprocess.
 14. The on-body injector system of claim 13, wherein thebarrier includes a shoulder configured to obstruct the rays of radiationemitted by the radiation generator from interacting with the at least aportion of the container during the sterilization or disinfectionprocess.
 15. The on-body injector system of claim 1, wherein the barriersurrounds at least a portion of the seal interface.
 16. The on-bodyinjector system of claim 1, wherein: the seal member includes a firstsurface and a second surface located on opposite sides of the sealmember; the first surface of the seal member and a wall of the containerdefine a reservoir; and in the storage position, the point of the needleis disposed adjacent to the second surface of the seal member with nostructure in between the second surface of the seal member and the pointof the needle.
 17. An injector system comprising: a drug containerassembly including a container, a seal member, and a sealing interfacebetween the seal member and the container, the container having anopening and the seal member at least partially covering the opening inthe container; a fluid pathway assembly coupled to the drug containerassembly and including a needle, the needle being movable between astorage position, in which a point of the needle is spaced from the sealmember, and a delivery position, in which the point of the needle isdisposed at least partially through the seal member; a radiationgenerator; a wall disposed adjacent to the sealing interface and havingan opening, at least a portion of the drug container assembly beingpositioned adjacent to the opening in the wall; and wherein the sealinginterface is positioned to be sterilized or disinfected by radiationfrom the radiation generator.